Colorectal cancer is the second most common cause of cancer death in the United States. Both genetic and environmental factors appear to contribute to risk of colon cancer, supporting the possibility that interactions among these factors might also increase risk. In this project we are undertaking a case-control study of genetic and environmental (e.g., nutritional) risk factors for adenomatous polyps of the large bowel (precursors to colorectal cancer). Subjects are asymptomatic persons who attended a sigmoidoscopy screening clinic at one of two Kaiser Permanente-Southern California clinical centers. Cases are persons with a first-time diagnosis of at least one adenomatous polyp confirmed by biopsy. Controls are subjects found to have no adenomatous polyps at sigmoidoscopy and with no history of large bowel neoplasia. Results from the first stage of this study include inverse associations between high fiber foods (e.g., vegetables) and positive associations for animal sources of fat (as well as red meat). In the present stage we are investigating gene-environment interactions, including both "inherited susceptibility genes" and "metabolic genes" (i.e., hMSH2, NAT2, and GST1). Currently, we are doubling the sample size of this study to 1200 cases and 1200 controls.